16-15643555-AC-A

Position:

• chr16-15643555-AC-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000396355.5(NDE1):​c.-535del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0111 in 324,396 control chromosomes in the GnomAD database, including 141 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.023 (141 hom., cov: 31)
  • Exomes 𝑓: 0.0010 (0 hom.)
• Consequence: NDE1 ENST00000396355.5 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.15

Genes affected

NDE1 (HGNC:17619): (nudE neurodevelopment protein 1) This gene encodes a member of the nuclear distribution E (NudE) family of proteins. The encoded protein is localized at the centrosome and interacts with other centrosome components as part of a multiprotein complex that regulates dynein function. This protein plays an essential role in microtubule organization, mitosis and neuronal migration. Mutations in this gene cause lissencephaly 4, a disorder characterized by lissencephaly, severe brain atrophy, microcephaly, and severe cognitive disability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2012]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 16-15643555-AC-A is Benign according to our data. Variant chr16-15643555-AC-A is described in ClinVar as [Likely_benign]. Clinvar id is 318023.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0782 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDE1	NM_001143979.2	c.-535del		5_prime_UTR_variant	1/10		NP_001137451.1
NDE1	XM_006720897.5	c.-317del		5_prime_UTR_variant	1/8		XP_006720960.1
NDE1	XM_047434258.1	c.-317del		5_prime_UTR_variant	1/8		XP_047290214.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDE1	ENST00000396355.5	c.-535del		5_prime_UTR_variant	1/10	1		ENSP00000379643	P1

Frequencies

GnomAD3 genomes AF: 0.0233 AC: 3430 AN: 146942 Hom.: 141 Cov.: 31

Gnomad AFR AF: 0.0806

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00964

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000431

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000465

Gnomad OTH AF: 0.0171

GnomAD4 exome AF: 0.00101 AC: 179 AN: 177406 Hom.: 0 Cov.: 0 AF XY: 0.000797 AC XY: 82 AN XY: 102948

Gnomad4 AFR exome AF: 0.0644

Gnomad4 AMR exome AF: 0.00529

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000152

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000370

Gnomad4 OTH exome AF: 0.00512

GnomAD4 genome AF: 0.0233 AC: 3432 AN: 146990 Hom.: 141 Cov.: 31 AF XY: 0.0229 AC XY: 1635 AN XY: 71502

Gnomad4 AFR AF: 0.0805

Gnomad4 AMR AF: 0.00956

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000433

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000465

Gnomad4 OTH AF: 0.0170

Alfa AF: 0.0177 Hom.: 11

Bravo AF: 0.0254

Asia WGS AF: 0.00404 AC: 14 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Lissencephaly, Recessive Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs146418251; hg19: chr16-15737412;